Possible expression of a particular gamma-aminobutyric acid transporter isoform responsive to upregulation by hyperosmolarity in rat calvarial osteoblasts

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• 作者：Sayumi Fujimori ; Eiichi Hinoi ; Takeshi Takarada ; Mika Iemata ; Yoshifumi Takahata and Yukio Yoneda
• 关键词：GABA ; Betaine/GABA transporter ; Osteoblast ; [³H]GABA accumulation
• 刊名：European Journal of Pharmacology
• 出版年：2006
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：21 November 2006
• 卷：550
• 期：1-3
• 页码：24-32
• 文件大小：455 K

摘要

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the brain, but widely distributed in different peripheral organs. We have previously shown the functional expression of GABA_B receptors required for GABAergic signal input by cultured rat calvarial osteoblasts. This study focused on the possible functional expression of the machinery required for GABAergic signal termination such as GABA transporters. In rat calvarial osteoblasts cultured for 7 days, [³H]GABA accumulation was observed in a temperature-, sodium- and chloride-dependent manner, consisting of a single component with a K_m value of 789.6 ± 9.0 μM and a V_max value of 4.4 ± 0.1 nmol/min/mg protein, respectively. Both nipecotic and l-2,4-diaminobutyric acids significantly inhibited [³H]GABA accumulation in a concentration-dependent manner. Constitutive expression was seen with mRNA for the betaine/GABA transporter-1 (BGT-1) and taurine transporter (TauT), while hyperosmotic cultivation led to significant increases in both [³H]GABA accumulation and BGT-1 mRNA expression without affecting TauT mRNA expression. Highly immunoreactive cells were detected for the BGT-1 isoform at the surface of trabecular bone of neonatal rat tibias. Sustained exposure to GABA significantly inhibited alkaline phosphatase (ALP) activity, but not cellular viability, at concentrations above 0.1 mM in osteoblasts cultured for 3 to 28 days. Nipecotic acid not only decreased ALP activity alone, but also further decreased ALP activity in osteoblasts cultured in the presence of GABA. These results suggest that the BGT-1 isoform may be functionally expressed by rat calvarial osteoblasts to play a hitherto unidentified role in mechanisms underlying hyperosmotic regulation of osteoblastogenesis.